Myxomatous Mitral Valve Disease in Large Breed Dogs: Survival Characteristics and Prognostic Variables.

Myxomatous mitral valve disease (MMVD) is the most common acquired heart disease in dogs and its occurrence in small-and medium-sized dogs has been extensively investigated. MMVD has been described in large breed dogs as well, but substantial knowledge gaps remain. The aim of this study was to provide characteristics, survival times, and prognostic variables in large breed dogs with MMVD. Medical records of dogs diagnosed with MMVD, between 2012 and 2021, were retrospectively reviewed and 202 dogs were analyzed. Median survival time (MST) for all-cause mortality was 800 days for stage B1 dogs, 274 days for stage B2 dogs, and 184 days for stage C dogs. The MST for cardiac-related death for B1 dogs could not be calculated (because survival was greater than 50% at the last timepoint) and for stage B2 and C dogs the MST were 484 and 252 days, respectively. These findings suggest that the frequency of cardiac-related death is low in large breed dogs with stage B1 MMVD. In addition, increased left atrial and ventricular size, evidence of systolic dysfunction, a thrilling murmur, and increased early trans-mitral peak velocity are predictors of cardiac-related death. Data also suggest that the risk of a negative outcome increases profoundly when large breed dogs advance from ACVIM stage B1 into stage B2 or C.

Spatiotemporal lower-limb asymmetries during stair descent in athletes following anterior cruciate ligament reconstruction.

PURPOSE: This study evaluated motor control recovery at different times following anterior cruciate ligament reconstruction (ACLR) by investigating lower-limb spatiotemporal symmetry during stair descent performances. METHODS: We used a cross-sectional design to compare asymptomatic athletes (Controls, n = 18) with a group of people with ACLR (n = 49) divided into three time-from-ACLR subgroups (Early: <6 months, n = 17; Mid: 6-18 months, n = 16; Late: ≥18 months, n = 16). We evaluated: "temporal symmetry" during the stance subphases (single-support, first and second double-support) and "spatial symmetry" for hip-knee-ankle intra-joint angular displacements during the stance phase using a dissimilarity index applied on superimposed 3D phase plots. RESULTS: We found significant between-group differences in temporal variables (p ≤ 0.001). Compared to Controls, both Early and Mid (p ≤ 0.05) showed asymmetry in the first double-support time (longer for their injured vs. non-injured leg), while Early generally also showed longer durations in all other phases, regardless of stepping leg. No statistically significant differences were found for spatial intra-joint symmetry between groups. CONCLUSION: Temporal but not spatial asymmetry in stair descent is often present early after ACLR; it may remain for up to 18 months and may underlie subtle intra- and inter-joint compensations. Spatial asymmetry may need further exploration.

Right hemisphere brain lateralization for knee proprioception among right-limb dominant individuals.

Introduction: Studies indicate that brain response during proprioceptive tasks predominates in the right hemisphere. A right hemisphere lateralization for proprioception may help to explain findings that right-limb dominant individuals perform position matching tasks better with the non-dominant left side. Evidence for proprioception-related brain response and side preference is, however, limited and based mainly on studies of the upper limbs. Establishing brain response associated with proprioceptive acuity for the lower limbs in asymptomatic individuals could be useful for understanding the influence of neurological pathologies on proprioception and locomotion. Methods: We assessed brain response during an active unilateral knee joint position sense (JPS) test for both legs of 19 right-limb dominant asymptomatic individuals (females/males = 12/7; mean ± SD age = 27.1 ± 4.6 years). Functional magnetic resonance imaging (fMRI) mapped brain response and simultaneous motion capture provided real-time instructions based on kinematics, accurate JPS errors and facilitated extraction of only relevant brain images. Results: Significantly greater absolute (but not constant nor variable) errors were seen for the dominant right knee (5.22° ± 2.02°) compared with the non-dominant left knee (4.39° ± 1.79°) (P = 0.02). When limbs were pooled for analysis, significantly greater responses were observed mainly in the right hemisphere for, e.g., the precentral gyrus and insula compared with a similar movement without position matching. Significant response was also observed in the left hemisphere for the inferior frontal gyrus pars triangularis. When limbs were assessed independently, common response was observed in the right precentral gyrus and superior frontal gyrus. For the right leg, additional response was found in the right middle frontal gyrus. For the left leg, additional response was observed in the right rolandic operculum. Significant positive correlations were found between mean JPS absolute errors for the right knee and simultaneous brain response in the right supramarginal gyrus (r = 0.464, P = 0.040). Discussion: Our findings support a general right brain hemisphere lateralization for proprioception (knee JPS) of the lower limbs regardless of which limb is active. Better proprioceptive acuity for the non-dominant left compared with the dominant right knee indicates that right hemisphere lateralization may have meaningful implications for motor control.

Brain Response to a Knee Proprioception Task Among Persons With Anterior Cruciate Ligament Reconstruction and Controls.

Knee proprioception deficits and neuroplasticity have been indicated following injury to the anterior cruciate ligament (ACL). Evidence is, however, scarce regarding brain response to knee proprioception tasks and the impact of ACL injury. This study aimed to identify brain regions associated with the proprioceptive sense of joint position at the knee and whether the related brain response of individuals with ACL reconstruction differed from that of asymptomatic controls. Twenty-one persons with unilateral ACL reconstruction (mean 23 months post-surgery) of either the right (n = 10) or left (n = 11) knee, as well as 19 controls (CTRL) matched for sex, age, height, weight and current activity level, performed a knee joint position sense (JPS) test during simultaneous functional magnetic resonance imaging (fMRI). Integrated motion capture provided real-time knee kinematics to activate test instructions, as well as accurate knee angles for JPS outcomes. Recruited brain regions during knee angle reproduction included somatosensory cortices, prefrontal cortex and insula. Neither brain response nor JPS errors differed between groups, but across groups significant correlations revealed that greater errors were associated with greater ipsilateral response in the anterior cingulate (r = 0.476, P = 0.009), supramarginal gyrus (r = 0.395, P = 0.034) and insula (r = 0.474, P = 0.008). This is the first study to capture brain response using fMRI in relation to quantifiable knee JPS. Activated brain regions have previously been associated with sensorimotor processes, body schema and interoception. Our innovative paradigm can help to guide future research investigating brain response to lower limb proprioception.

An obstacle clearance test for evaluating sensorimotor control after anterior cruciate ligament injury: A kinematic analysis.

Sensorimotor deficits, particularly proprioceptive, are often reported following rupture of the anterior cruciate ligament (ACL). High secondary injury rates and long-term negative consequences suggest that these deficits are not properly identified using current assessment methods. We explored a novel obstacle clearance test to evaluate sensorimotor control in individuals following ACL reconstruction (ACLR) and rehabilitation. Thirty-seven post-ACLR individuals, 23 nonathletic asymptomatic controls (CTRL), and 18 elite athletes stepped over a hurdle-shaped obstacle, downward vision occluded, aiming for minimal clearance. Kinematic outcomes (3D motion capture) for the leading and trailing legs, for two unpredictably presented obstacle heights, were categorized into Accuracy: vertical foot clearance and minimal distance from the obstacle; Variability: end-point and hip/knee trajectory; and Symmetry: trunk/hip/knee crossing angles, hip-knee-ankle movement, and velocity curves. Accuracy was worse for CTRL compared with both other groups. ACLR had less leading and trailing vertical foot clearance with their injured compared with their noninjured leg. ACLR and athletes had less crossing knee flexion in their injured/nondominant legs compared with their contralateral leg, both leading and trailing. ACLR showed greater trunk flexion when crossing with their injured leg, both leading and trailing. For the leading leg, ACLR showed greater asymmetry for the hip-knee-ankle velocity curve compared with elite athletes. Trailing leg trajectory variability was lower for ACLR compared with CTRL and athletes for higher obstacles. Clinical significance: Sensorimotor deficits in individuals post-ACLR were reflected by greater asymmetry and less variable (more stereotypical) trajectories rather than limb positioning ability. This consideration should be addressed in clinical evaluations.

Evaluation of Concurrent Validity between a Smartphone Self-Test Prototype and Clinical Instruments for Balance and Leg Strength.

The evolving use of sensors to objectively assess movements is a potentially valuable addition to clinical assessments. We have developed a new self-test application prototype, MyBalance, in the context of fall prevention aimed for use by older adults in order to independently assess balance and functional leg strength. The objective of this study was to investigate the new self-test application for concurrent validity between clinical instruments and variables collected with a smartphone. The prototype has two test procedures: static standing balance test in two positions, and leg strength test performed as a sit-to-stand test. Thirty-one older adults were assessed for balance and functional leg strength, in an outpatient physiotherapy setting, using seven different clinical assessments and three sensor-tests. The results show that clinical instruments and sensor measurements correlate to a higher degree for the smartphone leg strength test. For balance tests, only a few moderate correlations were seen in the Feet Together position and no significant correlations for the Semi Tandem Stance. This study served as a first step to develop a smartphone self-test application for older adults to assess functional balance at home. Further research is needed to test validity, reliability, and user-experience of this new self-test application.

Influence of visual feedback, hand dominance and sex on individuated finger movements.

The ability to perform individual finger movements, highly important in daily activities, involves visual monitoring and proprioception. We investigated the influence of vision on the spatial and temporal control of independent finger movements, for the dominant and non-dominant hand and in relation to sex. Twenty-six healthy middle-aged to old adults (M age = 61 years; range 46-79 years; females n = 13) participated. Participants performed cyclic flexion-extension movements at the metacarpophalangeal joint of one finger at a time while keeping the other fingers as still as possible. Movements were recorded using 3D optoelectronic motion technique (120 Hz). The movement trajectory distance; speed peaks (movement smoothness); Individuation Index (II; the degree a finger can move in isolation from the other fingers) and Stationarity Index (SI; how still a finger remains while the other fingers move) were extracted. The main findings were: (1) vision only improved the II and SI marginally; (2) longer trajectories were evident in the no-vision condition for the fingers of the dominant hand in the female group; (3) longer trajectories were specifically evident for the middle and ring fingers within the female group; (4) females had marginally higher II and SI compared with males; and (5) females had fewer speed peaks than males, particularly for the ring finger. Our results suggest that visual monitoring of finger movements marginally improves performance of our non-manipulative finger movement task. A consistent finding was that females showed greater independent finger control compared with males.

Validation of a Mitotic Index Cutoff as a Prognostic Marker in Undifferentiated Uterine Sarcomas.

Undifferentiated uterine sarcomas (UUS) are a heterogenous group of high-grade mesenchymal tumors. Although these tumors are highly aggressive, a subset of patients may experience long-term survival. These tumors have previously been divided morphologically into uniform and pleomorphic types. A previous study demonstrated that a mitotic index cutoff of 25 mitoses/10 high-power fields (corresponding to 11.16 mitotic figures/mm) could successfully divide tumors into 2 prognostic groups with significantly different overall survival. The goals of the current study were to (1) validate this mitotic index cutoff in an independent, multicenter cohort and (2) explore the prognostic value of the mitotic index groups in relation to other clinicopathologic variables. Cases were included from 3 independent institutions: The Norwegian Radium Hospital, The Mayo Clinic, and Skåne University Hospital. A total of 40 tumors were included after central review. All cases were negative for the YWHAE-FAM22A/B and JAZF1-JJAZ1 translocations. Survival data were available on all patients. In this study, one-third of patients with UUS survived beyond 5 years. The crude (unadjusted) Cox Proportional Hazards model revealed a number of parameters that significantly impacted overall survival, including mitotic index group, patient age, stage, and the presence of tumor necrosis. Classification into the uniform and pleomorphic types was not prognostic. Combining these parameters into an adjusted model revealed that only the mitotic index group and stage were prognostic. On the basis of these findings, it is proposed that UUS be subdivided into "mitogenic" and "not otherwise specified" types.

A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis.

Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53, and DNA ploidy. A representative H&E slide was scanned digitally and made available to 12 gynecologic pathologists in 4 Nordic countries: Finland, Denmark, Sweden, and Norway. Reviewers diagnosed the cases both before and after being provided with the biomarker results. The interobserver percent agreement and Cohen κ improved from 75.8% (κ=0.52, moderate) to 84% (κ=0.68, substantial) with inclusion of the biomarker panel. Agreement with the subsequent hysterectomy diagnosis also improved from 83.6% (κ=0.67) to 88.7% (κ=0.77). There was no statistical improvement between a reflex (84% agreement) and a reflective testing algorithm (82.9% agreement), suggesting that the selective use of biomarkers is appropriate. Difficult cases were almost exclusively high-grade tumors. Finally, a statistical model indicated that only P53 and DNA ploidy, in conjunction with an H&E review, had an impact on the decision to upgrade or downgrade cases.

A prognosis based classification of undifferentiated uterine sarcomas: identification of mitotic index, hormone receptors and YWHAE-FAM22 translocation status as predictors of survival.

Undifferentiated uterine sarcomas (UUS) are rare tumors with a heterologous biology and a poor prognosis. The goal of this study was to examine clinicopathology, biomarkers and YWHAE-FAM22 translocation status, in the prognosis of these tumors. Twenty-six cases of UUS were included. All original slides were rereviewed and age at diagnosis, tumor stage, "Kurihara" diagnosis, mitotic index, presence of necrosis and grade of nuclear atypia were recorded. Additionally, a tissue microarray was constructed from 22 of the cases, and the protein biomarkers P53, P16, Ki-67, Cyclin-D1, ER, PR and ANLN were evaluated by immunohistochemistry. All tumors were evaluated for the presence of a YWHAE-FAM translocation; the translocation was demonstrated in the three Cyclin-D1 positive tumors. Follow-up data in the form of overall survival were available on all patients. These tumors could be divided into two prognostic groups, a high mitotic index group (10 cases, M = 36.8, SD = 5.4) and a low mitotic index group (16 cases, M = 8.7, SD = 5.8). These two groups showed a statistically significant difference in prognosis. The expression of ER, PR or presence of the YWHAE-FAM22 translocation correlated with low mitotic index and an additionally improved prognosis, although the number of cases was small. These results indicate that UUS can be divided into two prognostic groups using mitotic index as a primary criteria, followed by expression of either ER, PR or the presence of a YWHAE-FAM22 translocation as a secondary criteria. This study demonstrates the presence of statistically significant prognostic subgroups within UUS, and provides treatment insights.